Makita R, Mizuno T, Koshida S, Kuroiwa A, Takeda H
Division of Biological Science, Graduate School of Science, Nagoya University, Japan.
Mech Dev. 1998 Feb;71(1-2):165-76. doi: 10.1016/s0925-4773(98)00013-6.
This study analyzed the spatial and temporal expression pattern of zebrafish wnt11 and the regulation of the expression during zebrafish early development, focusing on the interaction with the no tail (ntl) gene, a zebrafish orthologue of mouse Brachyury (T). Zygotic expression of wnt11 was first detected at the late blastula stage in the blastoderm margin, a presumptive mesoderm region. wnt11 expression coincided with mesoderm induction, and the expression was induced by mesoderm inducers such as the yolk cell (Mizuno, T., Yamaha, E., Wakahara, M., Kuroiwa, A., Takeda, H., 1996. Mesoderm induction in zebrafish. Nature 383, 131-132) or FGFs, indicating that, like ntl, wnt11 is one of the immediate-early genes in mesoderm induction. Initial expression domains of wnt11 and ntl overlapped, and these genes showed a similar response to mesoderm inducers. However, analysis of the ntl mutant embryos suggested that wnt11 and ntl are placed in distinct genetic pathways; the ntl mutation had no effect on wnt11 expression in the blastoderm margin. This was further supported by the result of RNA injection experiments showing that overexpression of Wnt11 did not affect ntl expression in the margin. Thus, wnt11 and ntl expression are induced and maintained independently in their initial phase of expression. In later stages, wnt11 was expressed in various organs, such as the somites, particularly in the developing notochord. Since no wnt gene has been reported to be expressed in the axial mesoderm, which is known to act as a signaling source that patterns the neural tube and somites, zebrafish wnt11 is the first wnt gene expressed in the notochord. Furthermore, in contrast to early expression, wnt11 expression in the notochord depended on Ntl activity. In the ntl mutant in which somite patterning is severely affected, wnt11 expression was completely lost, while another signaling molecule, sonic hedgehog is expressed in the mutant notochord precursor cells (Krauss, S., Concordet, J.-P., Ingham, P.W., 1993. A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos. Cell 75, 1431-1444). wnt11 expression in the somite also shows a characteristic pattern, correlated with the migration and differentiation of slow muscle precursors. These observations suggest a role for wnt11 in patterning the somites.
本研究分析了斑马鱼wnt11的时空表达模式以及在斑马鱼早期发育过程中该表达的调控,重点关注其与无尾(ntl)基因的相互作用,ntl基因是小鼠短尾(T)基因在斑马鱼中的同源基因。wnt11的合子表达最初在囊胚晚期的胚盘边缘被检测到,该区域是假定的中胚层区域。wnt11的表达与中胚层诱导同时发生,并且该表达由中胚层诱导因子如卵黄细胞(水野彻、山 Yamaha、若原真、黑岩明、武田浩,1996年。斑马鱼的中胚层诱导。《自然》383卷,131 - 132页)或成纤维细胞生长因子诱导,这表明,与ntl一样,wnt11是中胚层诱导中的即时早期基因之一。wnt11和ntl的初始表达域重叠,并且这些基因对中胚层诱导因子表现出相似的反应。然而,对ntl突变胚胎的分析表明,wnt11和ntl处于不同的遗传途径;ntl突变对胚盘边缘的wnt11表达没有影响。RNA注射实验结果进一步支持了这一点,该结果表明Wnt11的过表达不影响边缘区域的ntl表达。因此,wnt11和ntl的表达在其表达的初始阶段是独立诱导和维持的。在后期阶段,wnt11在各种器官中表达,如体节,特别是在发育中的脊索中。由于尚未有报道称任何wnt基因在轴向中胚层中表达,而轴向中胚层已知作为一种信号源对神经管和体节进行模式化,斑马鱼wnt11是第一个在脊索中表达的wnt基因。此外,与早期表达相反,wnt11在脊索中的表达依赖于Ntl活性。在体节模式严重受影响的ntl突变体中,wnt11表达完全丧失,而另一种信号分子音猬因子在突变体的脊索前体细胞中表达(克劳斯、康科德、英厄姆,1993年。果蝇节段极性基因hh的功能保守同源物在斑马鱼胚胎中具有极化活性的组织中表达。《细胞》75卷,1431 - 1444页)。wnt11在体节中的表达也呈现出一种特征模式,与慢肌前体细胞的迁移和分化相关。这些观察结果表明wnt11在体节模式化中发挥作用。